Human Embryonic Stem Cell-Derived Mesenchymal Stroma Cells (hES-MSCs) Engraft In Vivo and Support Hematopoiesis without Suppressing Immune Function: Implications for Off-The Shelf ES-MSC Therapies

Abstract

Mesenchymal stroma cells (MSCs) have a high potential for novel cell therapy approaches in clinical transplantation. Commonly used bone marrow-derived MSCs (BM-MSCs), however, have a restricted proliferative capacity and cultures are difficult to standardize. Recently developed human embryonic stem cell-derived mesenchymal stroma cells (hES-MSCs) might represent an alternative and unlimited source of hMSCs. We therefore compared human ES-cell-derived MSCs (hES-MP002.5 cells) to normal human bone marrow-derived MSCs (BM-MSCs). hES-MP002.5 cells had lower yet reasonable CFU-F capacity compared with BM-MSC (8±3 versus 29±13 CFU-F per 100 cells). Both cell types showed similar immunophenotypic properties, i.e. cells were positive for CD105, CD73, CD166, HLA-ABC, CD44, CD146, CD90, and negative for CD45, CD34, CD14, CD31, CD117, CD19, CD 271, SSEA-4 and HLA-DR. hES-MP002.5 cells, like BM-MSCs, could be differentiated into adipocytes, osteoblasts and chondrocytes in vitro. Neither hES-MP002.5 cells nor BM-MSCs homed to the bone marrow of immune-deficient NSG mice following intravenous transplantation, whereas intra-femoral transplantation into NSG mice resulted in engraftment for both cell types. In vitro long-term culture-initiating cell assays and in vivo co-transplantation experiments with cord blood CD34+ hematopoietic cells demonstrated furthermore that hES-MP002.5 cells, like BM-MSCs, possess potent stroma support function. In contrast to BM-MSCs, however, hES-MP002.5 cells showed no or only little activity in mixed lymphocyte cultures and phytohemagglutinin (PHA) lymphocyte stimulation assays. In summary, ES-cell derived MSCs might be an attractive unlimited source for stroma transplantation approaches without suppressing immune function.

Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Are Functionally and Genetically Different From Bone Marrow-Derived Mesenchymal Stromal Cells

“…C). Of note, this immunophenotype was also observed in PSC‐MSC lines from other studies . We found that continued expansion could induce a dynamic expression pattern of CD90 in the cells (Supporting Information Fig.…”

Characterization and evaluation of mesenchymal stem cells derived from human embryonic stem cells and bone marrow

“…We also found that H1-MSCs and WA1-MSCs express a lower level of CD90 than BM-MSCs. This has also been demonstrated in studies using different ESC-MSC lines by other groups (Hwang et al 2008b; Li et al 2013; Varga et al 2011; Yen, et al 2011), and these cell lines demonstrate varying potential of differentiation compared to BM-MSCs. In this study, lower expression of CD90 and CD106 in ESC-MSCs may be correlated to less potent multi-lineage differentiation.…”

Differentiation of Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells Results in Downregulation of c-Myc and DNA Replication Pathways with Immunomodulation Toward CD4 and CD8 Cells

“…While findings are consistent regarding the multilineage capacity of PSC‐MSCs , reports on the immunomodulatory properties of these MSCs have been few and discrepant. MSCs derived from human ESCs (ESC‐MSCs) were the first to be reported on, and with the exception of one study in which only one cell line was used , nearly all studies have found significant immunomodulatory effects for these MSCs . On the other hand, data on iPSC‐MSC immunomodulation have ranged from immunosuppression to no effect , to immunoreactive .…”